scholarly journals Guanylate-binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-γ and regulates barrier function through effects on apoptosis

2008 ◽  
Vol 2 (1) ◽  
pp. 33-42 ◽  
Author(s):  
M Schnoor ◽  
A Betanzos ◽  
D A Weber ◽  
C A Parkos
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Interferon Γ ◽  
Intestinal Epithelial ◽  
Guanylate Binding Protein

scholarly journals JunD Represses Transcription and Translation of the Tight Junction Protein Zona Occludens-1 Modulating Intestinal Epithelial Barrier Function

2008 ◽  
Vol 19 (9) ◽  
pp. 3701-3712 ◽  
Author(s):  
Jie Chen ◽  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Mrna Translation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO-1 mRNA translation by enhancing the interaction of the ZO-1 3′-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.

scholarly journals The JAK-Inhibitor Tofacitinib Rescues Human Intestinal Epithelial Cells and Colonoids from Cytokine-Induced Barrier Dysfunction

2019 ◽  
Vol 26 (3) ◽  
pp. 407-422 ◽  
Author(s):  
Anica Sayoc-Becerra ◽  
Moorthy Krishnan ◽  
Shujun Fan ◽  
Jossue Jimenez ◽  
Rebecca Hernandez ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junctions ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Janus Kinase ◽  
Intestinal Epithelial ◽  
Jak Inhibitor ◽  
Barrier Dysfunction ◽  
Ifn Γ

Abstract Background Alterations to epithelial tight junctions can compromise the ability of the epithelium to act as a barrier between luminal contents and the underlying tissues, thereby increasing intestinal permeability, an early critical event in inflammatory bowel disease (IBD). Tofacitinib (Xeljanz), an orally administered pan-Janus kinase (JAK) inhibitor, was recently approved for the treatment of moderate to severe ulcerative colitis. Nevertheless, the effects of tofacitinib on intestinal epithelial cell functions are largely unknown. The aim of this study was to determine if JAK inhibition by tofacitinib can rescue cytokine-induced barrier dysfunction in intestinal epithelial cells (IECs). Methods T84 IECs were used to evaluate the effects of tofacitinib on JAK-signal transducer and activator of transcription (STAT) activation, barrier permeability, and expression and localization of tight junction proteins. The impact of tofacitinib on claudin-2 promoter activity was assessed in HT-29 IECs. Tofacitinib rescue of barrier function was also tested in human colonic stem cell-derived organoids. Results Pretreatment with tofacitinib prevented IFN-γ-induced decreases in transepithelial electrical resistance (TER) and increases in 4 kDa FITC-dextran permeability (FD4), partly due to claudin-2 transcriptional regulation and restriction of ZO-1 rearrangement at tight junctions. Although tofacitinib administered after IFN-γ challenge only partially normalized TER and claudin-2 levels, FD4 permeability and ZO-1 localization were fully recovered. The IFN-γ-induced FD4 permeability in primary human colonoids was fully rescued by tofacitinib. Conclusions These data suggest differential therapeutic efficacy of tofacitinib in the rescue of pore vs leak-tight junction barrier defects and indicate a potential contribution of improved epithelial barrier function to the beneficial effects of tofacitinib in IBD patients.

The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells

Fitoterapia ◽  
2009 ◽  
Vol 80 (4) ◽  
pp. 241-248 ◽  
Author(s):  
Lili Gu ◽  
Ning Li ◽  
Qiurong Li ◽  
Qiang Zhang ◽  
Chengyang Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

scholarly journals Transcriptional regulation of importin-α1 by JunD modulates subcellular localization of RNA-binding protein HuR in intestinal epithelial cells

2016 ◽  
Vol 311 (6) ◽  
pp. C874-C883 ◽  
Author(s):  
Yan Xu ◽  
Jie Chen ◽  
Lan Xiao ◽  
Hee Kyoung Chung ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Subcellular Localization ◽  
Rna Binding ◽  
Nuclear Translocation ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Intestinal Epithelial ◽  
Mucosal Regeneration ◽  
Importin Α

The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1 expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1 at the transcription level, and this repression is mediated via interaction with CREB-binding site that was located at the proximal region of importin-α1 promoter. Reduction in the levels of importin-α1 by JunD increased cytoplasmic levels of HuR, although it failed to alter whole cell HuR levels. Increased levels of endogenous JunD by depleting cellular polyamines also inhibited importin-α1 expression and increased cytoplasmic HuR levels, whereas JunD silencing rescued importin-α1 expression and enhanced HuR nuclear translocation in polyamine-deficient cells. Moreover, importin-α1 silencing protected IECs against apoptosis, which was prevented by HuR silencing. These results indicate that JunD regulates HuR subcellular distribution by downregulating importin-α1, thus contributing to the maintenance of gut epithelium homeostasis.

Co-operation of interleukin-17 and interferon-γ on chemokine secretion in human fetal intestinal epithelial cells

2001 ◽  
Vol 120 (5) ◽  
pp. A189
Author(s):  
Hiroki Takaya ◽  
Akira Andoh ◽  
Jin Makino ◽  
Takashi Okuno ◽  
Kazunori Hata ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Intestinal Epithelial
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